Non-invasive periocular device for dry-eye treatment

ABSTRACT

A periocular ring configured to be worn on an eye of a user that includes a plurality of electrodes spaced along the periocular ring; a microcontroller; and a lead assembly extending along at least a portion of the periocular ring; wherein the lead assembly extends between the microcontroller and the plurality of electrodes to operably couple the plurality of electrodes to the microcontroller; and wherein the microcontroller is configured to activate the plurality of electrodes via the lead assembly to stimulate a lacrimal gland of the user. The periocular ring has an opening that defines an innermost diameter; and wherein, when the periocular ring is worn on the eye of the user, a portion of the eye extends through the opening of the periocular ring.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.16/829,563, filed Mar. 25, 2020, which claims the benefit of the filingdate of, and priority to, U.S. Application No. 62/824,111, filed Mar.26, 2019, the entireties of which are hereby incorporated herein byreference.

BACKGROUND

A large number of people have Dry Eye Disease (“DED”), which includessymptoms of intense pain, stinging eyes, foreign body sensation, lightsensitivity, blurriness, increased risk of infection, and possiblevision loss.

DED is characterized by insufficient tear volume on the ocular surfaceof a patient, which is generally caused by insufficient tear productionor excessive tear evaporation. Insufficient tear volume results in tearhyperosmolarity, which causes inflammation and nerve damage and can leadto progressive loss of tear production and quality.

Dry-eye symptoms vary based on a variety of factors. For example,dry-eye symptoms vary throughout a day in response to diurnalphysiological variations in tear pH, intraocular pressure, cornealsensitivity, visual sensitivity, and melatonin production. For instance,corneal sensitivity is often significantly greater in the evening thancompared to the morning. Longer term variations in dry-eye symptoms canbe related to use of systemic medications, chronic disease (e.g.,diabetes), hormonal changes, and aging. Changes to a patient'senvironment also contribute to dry-eye symptom variations. For example,dry-eye symptoms can increase due to low humidity of air-conditionedoffices, winter heating, computer use, phone use, allergens, and contactlenses.

Current approaches to treatment of dry-eye symptoms do not or cannotaccount for the variety of factors that impact the severity and onset ofthe symptoms, as current treatment for DED is primarily eye-drop basedand provides only limited episodic and temporary relief.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of a periocular device to be worn around aneye, and proximate to a lacrimal gland, of a user, according to anexample embodiment.

FIG. 2 is a diagrammatic illustration of the device of FIG. 1, accordingto an example embodiment.

FIG. 3 is a front view of an illustration including the device, the eye,and the lacrimal gland of FIG. 1, according to an example embodiment.

FIG. 4 is a side view of an illustration including the device, the eye,and the lacrimal gland of FIG. 1, according to an example embodiment.

FIG. 5 is an illustration of a sectional view of the device of FIG. 1,according to an example embodiment.

FIG. 6 is an illustration of a front view of the device of FIG. 1,according to an example embodiment.

FIG. 7 is a diagrammatic illustration of the device of FIG. 1, a remotedevice, and another remote device connected via a network, according toan example embodiment.

FIG. 8 is a flow chart illustrating a method of operating the device ofFIGS. 1-7, according to an example embodiment.

FIG. 9 is a flow chart illustrating a step in the method of FIG. 8,according to an example embodiment.

FIG. 10 is a diagrammatic illustration of a closed loop system formed bythe device of FIG. 1 during the method of FIG. 9, according to anexample embodiment.

FIG. 11 is a diagrammatic illustration of a node for implementing one ormore example embodiments of the present disclosure, according to anexample embodiment.

DETAILED DESCRIPTION

The following disclosure provides many different embodiments orexamples. Specific examples of components and arrangements are describedbelow to simplify the present disclosure. These are, of course, merelyexamples and are not intended to be limiting. In addition, the presentdisclosure may repeat reference numerals and/or letters in the variousexamples. This repetition is for the purpose of simplicity and clarityand does not in itself dictate a relationship between the variousembodiments and/or configurations discussed.

The present disclosure presents embodiments of a device with a uniqueform factor to provide dry-eye therapy. For example, embodiments of aring-shaped periocular neurostimulator are presented for stimulating thelacrimal gland to stimulate tear production. In at least someembodiments, the periocular device rests on the surface of the eye, sono surgical procedures or implanted or implantable devices are neededfor dry-eye therapy. Some advantages include that a patient can havespecific, non-invasive personalized dry-eye therapy delivered seamlesslythroughout the day, synchronized to the patient's natural circadianvariation, and personalized to the patient's environment. Further, aform factor of the device allows for sensor placement at differentpoints about the periphery or circumference of the device, allowing forclosed-loop control of stimulation, based on measurements related todryness of the eye, as discussed further herein.

A device generally referred to by the reference numeral 10, asillustrated in FIG. 1, is an example ring-shaped periocular device forneurostimulation. When mounted on the eye, the device 10 is not visibleor noticeable to the user or others. Moreover, the device 10 does notobstruct the view of the user, as the device 10 does not extend over thepupil, iris, limbal ring, etc. As such, the device 10 can be usedsimultaneously with traditional vision correction devices, such ascontact lenses and eye glasses. The device 10 is insertable in theperiocular space and easily removable for cleaning and/or recharging.Thus, insertion and removal of the device 10 can be performed withoutthe need for surgery. In some instances, the user can insert and removethe device 10 in his or her home. The device 10 also provides forhands-free stimulation. That is, as the device 10 includes electrodesfor stimulating the lacrimal gland and a microcontroller that controlsthe stimulation, and the user is not required to perform any activity toactivate the electrodes. The stimulation can be based on a predeterminedschedule that is stored in the device 10 or can be in response to adetected or predicted dry eye condition. For example, while the user isperforming another activity, such as viewing a graphical display of hisor her mobile phone, the camera of the mobile phone may detect a blinkrate that indicates the user is experiencing a dry-eye symptom. Inresponse, the mobile phone wirelessly instructs the device 10 toactivate the electrodes to stimulate the lacrimal gland. In someinstances, the user is not aware of the detection, instruction, andactivation. A user may utilize a device 10 in one eye or a device ineach eye (i.e., a user may use two devices 10, one for each eye), asneeded. For ease of description, the disclosure focuses on theapplication of device 10 to one eye, with the understanding that thedisclosure may apply to both eyes of a user.

In an example embodiment and as illustrated in FIG. 1, the device 10generally includes a wearable band or ring 15 and a gland stimulatorassembly 20. In some embodiments, the stimulator assembly 20 isconsidered part of the ring 15, as the stimulator assembly 20 isattached physically and electrically to the ring. The term “ring” usedherein refers generally to a substantially circular shape but it is notso limited and may refer to an elliptical shape circumscribing, andspaced from, portions of the eye, such as the limbal ring. Generally,the device 10 is configured to encircle the front of an eye 35 of a user40 in the ocular fornix area. For example, the device 10 may be wornoutside the periphery of a user's iris, circumscribing the iris, andspaced radially away from the iris. The device 10 is positioned suchthat the gland stimulator assembly 20 is in close enough proximity to alacrimal gland 55 of the user 40 to stimulate tear production whenelectrical signals are applied to the stimulator assembly. As isunderstood in the art, electrical stimulation of a lacrimal gland 55 isknown to increase tear production.

The disclosed devices, systems, and methods are for treating conditionsof a patient's DED using a chronotherapeutic approach. Thechronotherapeutic approach is implemented by the device 10, whichdelivers gland stimulation at the time when it is needed. That is, glandstimulation is synchronized with circadian rhythms, among other factors,in some embodiments. If the peak of symptoms occurs at daytime forexample, gland stimulation can be performed just before or when thesymptoms are worsening, depending on the delay between stimulation ofthe gland and production of additional tear fluid.

As illustrated in FIG. 2, the gland stimulator assembly 20 generallyincludes electrodes 21, a microcontroller 22, and a lead assembly 23that operably couples the electrodes 21 to the microcontroller 22.Generally, the microcontroller 22 also includes, or is operably coupledto, a power source 24 and a memory 26. In some embodiments and when thepower source 24 includes a battery, such as a lithium thionyl chloridecell, the battery has terminals connected to the input of a voltageregulator that forms a portion of the microcontroller 22. The regulatorsmooths the battery output and supplies power to the microcontroller 22,which controls the programmable functions of the stimulator assembly 20,including known stimulation parameters such as pulse amplitude (measuredas current or voltage, e.g., 500 μA to 25 mA), pulse frequency, pulsewidth, and on-time and off-time of the output pulses supplied to theelectrodes 21. The microcontroller 22 is programmable in that a patientprofile can be stored in the memory 26. Using the patient profile, themicrocontroller 22 modulates the electrical activity of the lacrimalgland to produce the treatment regimen applicable to the patient. Timingsignals for the logic and control functions of the generator areprovided by the memory 26.

In some embodiments, the patient profile stored in the memory 26includes a temporal model that details target stimulation parameters tobe applied over a period of time. In some embodiments, the targetstimulation parameters include a magnitude or charge density (e.g.,current or voltage), frequency, pulse width, on-time, and off-time ofthe output pulses. The temporal model could detail a treatment programthat is cycled daily, weekly, monthly, and/or seasonally. In someinstances, the temporal model is based on a monitored eye condition ofthe patient/user, a charting of perceived symptoms by the patient/user,and/or a generic temporal model based on patient: age, sex, weight,geographical location, profession, activity level, or any combinationthereof. Different combinations of stimulation parameters may beprogrammed into memory (e.g., by a clinician) and selectable by apatient. Patient selection of a combination of stimulation parametersmay take place via a software application on a smartphone andcommunicated to the ring 15 via Bluetooth or other form of wirelesscommunication. As other examples, the ring 15 may be configured fornear-field communication or inductive telemetry for communication with aprogramming wand.

In some embodiments, the electrodes 21 are located on the periphery ofthe ring 15 and are ideally located in apposition to the lacrimal gland55 or nerve when the device 10 is worn by the user 40. That is, when thedevice 10 is worn by the user 40, the microcontroller 22 applies anoutput signal to the gland 55 via the lead assembly 23 and theelectrodes 21. In some embodiments, the electrodes 21 are composed of amaterial including Pt, Pt/Ir alloys, Jr, and similar electrochemicallystable, high-charge capacity metals and alloys. In some embodiments,direct stimulation of the lacrimal gland 55 via the gland stimulatorassembly 20 dramatically increases tear production several fold. In someembodiments an as illustrated in FIGS. 5 and 6, the electrodes 21 arespaced along the ring 15. In some embodiments, the electrodes are spacedcircumferentially along the ring 15, spaced radially along the ring 15,and/or spaced circumferentially along a cross-section of the ring 15.For example, and referring to FIG. 5, electrodes 21 a and 21 b arespaced circumferentially and aligned radially along a cross-section ofthe ring 15 while electrodes 21 b and 21 c are spaced circumferentiallyand radially along the cross-section of the ring 15. Referring to FIG.6, electrodes 21 a and 21 d are spaced circumferentially along the ring15. In some embodiments, the electrodes 21 may be configured as anelectrode array for directing the generated electric field to moreeffectively stimulate the lacrimal gland.

In some instances, and as illustrated in FIGS. 3-6, the device 10includes a sensor assembly 58 that detects a dry-eye symptom to form aclosed-loop dry-eye treatment device. As such, the device 10 enables acustomized stimulation profile for treatment of DED. The frequency andduration of dry-eye symptoms are specific to each person with DEDbecause dry-eye symptoms are due to a wide variety of factors, such as,for example local environment, health-related issues, and time of day.As the device 10 detects and then treats the dry-eye symptoms, thedevice 10 is a closed-loop dry-eye treatment device 10. That is, thedevice 10 provides an automatic, customized treatment for DED and is achronotherapeutic neural stimulation system. Electronic stimulation ofthe lacrimal gland 55 and nerve is performed in a controlled manner onlywhen required and is based on physiological parameters measured by thedevice 10 and personalized or local environmental and health factors.

In some embodiments, the sensor assembly 58 includes one or more sensorsand/or types of sensors. For example, the sensor assembly 58 includessensors 58 a, 58 b, 58 c, and 58 d. For example, the sensor 58 a and 58b form a tear film break-up (“TFBU”) sensor system. Each of the sensors58 a and 58 b is a small electrode that are located about 180 degreesapart on the periphery of the ring 15. The electrode material may besuitable metals including Pt, Pt/Ir alloys, Jr, and similarelectrochemically stable metals. Generally, the sensors 58 a and 58 bmeasure resistivity of tear film that is located between the sensors 58a and 58 b during application of a small alternating current signal(e.g., 1-100 mV Pk-Pk) at frequencies above 1 kHz. At frequencies above1 kHz, the resultant signal is primarily a measure of the volumetricconductive path through tear fluid located on the eye 35 and as such isa function of the volume. As the tear film thins and breaks, acharacteristic AC impedance can be measured and correlated to tear-filmdynamics. These dynamics may include tear-film break-up time, rate ofevaporation, and total available volume. A faster break-up time is anindicator of overall dryness, including potential effects ofenvironmental factors. As such, the sensors 58 a and 58 b, whenconfigured to measure TFBU time, determine stability of the tear filmand determine evaporative dry eye based on resistivity of tear filmwithin an area 70. The sensors 58 a and 58 b are not required to bepositioned about 180 degrees apart on the periphery of the ring 15 andin some embodiments, the sensors 58 a and 58 b are spaced within 90degrees (along the periphery of the ring 15) to measure TFBU time withinan area smaller than the area 70. In some embodiments and when thesensors 58 a and 58 b are not spaced about 180 degrees apart, multiplepairings of sensors 58 a and 58 b are spaced around the periphery of thering 15, with each pair of sensor measuring an area or a portion of theeye 35. Together, the multiple pairings of sensors are used to determinetear-film dynamics of the eye 35.

In some embodiments, the sensor 58 c is or includes a microelectrode pHsensor that monitors tear pH levels, as tear osmolality and pH have beenshown to correlate with dry eyes. In some embodiments, the sensor 58 cis positioned along the ring 15 such that, when the ring 15 ispositioned around the eye 35, the sensor 58 c is positioned in the upperfornix, the lower fornix, and/or near the microcontroller 22 of thedevice 10 to ensure the sensor 58 c remains in contact with the tearfluid. In some embodiments, the sensor 58 c is factory-calibrated, butin other embodiments the microcontroller 22 makes patient-specificcalibrations performed with standard tear sampling materials in aclinician's office or through at-home systems. In some embodiments, theupper fornix area is between the eye 35 and the eyelid 45, and the lowerfornix area is between the eye 35 and the lower lid 50. However, in someinstances the upper fornix area is any upper area (e.g., toward theeyebrow of the user) adjacent to the eye 35 and the lower fornix area isany lower area (e.g., toward the jaw of the user) adjacent to the eye35.

In some embodiments and as illustrated in FIGS. 5 and 6, the sensor 58 dis a blink sensor. That is, the sensor 58 d is configured to monitor theblink rate of the user 40. Normal individuals display interblink timeson average 4±2 seconds, while patients with dry eye displaysignificantly decreased times averaging 1.5±0.9 seconds in an attempt tomaximize the tear supply to the ocular surface. Thus, blink rate can beused to identify a dry eye condition. In particular, the decrease ininterblink time for a specific patient can be measured throughout theday and used to correlate with diurnal variation in physiologicparameters such as corneal sensitivity. In some embodiments, the blinksensor 58 d includes a resonant circuit. In particular, the circuit maybe operated in a low-power configuration such that only start-upcharacteristics including start-up time or start-up current can beemployed as means to detect blink induced changes in the resonantcircuit response. In some embodiments, the resonant circuit includes anantenna 71 that is coupled to or forms a portion of the ring 15 and acapacitor 72 that is located within or near the electronics-containingbody of the device, or the microcontroller 22. In some embodiments, thesensor 58 d is an inductive-capacitive (LC) sensor that alters itscapacitance in response to physical movement of the eyelid 45 (i.e.,blinking), resulting in a shift in its resonant frequency. The change inresonant frequency is captured and processed by the integratedelectronics thereby providing an input signal that is correlated witheyelid movements.

In some embodiments, the ring 15 forms an opening and has an innerdiameter 15 a (shown in FIG. 3) that is generally within the range ofbetween about 24 mm to about 30 mm. However, the inner diameter 15 a maybe greater than 30 mm or less than about 24 mm. Generally, the ring 15contacts an ocular surface of the eye, with a portion of the eye 35extending through the opening of the ring 15. As illustrated, aninnermost surface of the ring 15 is spaced from a limbal ring 60 of theeye 35 by a distance 73 (shown in FIG. 3) such that the ring 15 ordevice 10 does not extend over the iris and/or the limbal ring 60 of theeye 35. As such, both the iris and the limbal ring 60 are unobstructedby the device 10. Generally, the distance 73 varies with movement of theeye 35. That is, the ring 15 remains generally stationary even as theeye 35 and the ocular surface move. In some embodiments, placementand/or movement of the ring 15 is independent from the movement of theeye 35. In some embodiments, the ring 15 has a generally consistentcross-sectional shape and size. However, in other embodiments, a portionof the ring 15 has a cross-sectional shape that is different than across-sectional shape of another portion of the ring 15. Moreover, theinner diameter 15 a of the ring 15 may vary independently from an outerdiameter of the ring 15.

In some embodiments and as illustrated in FIG. 5, a portion of the glandstimulator assembly 20 and/or a portion of the sensor assembly 58 aredisposed on a body of polymer substrate 66 to form the ring 15. Thepolymer substrate 66 may be composed of, or include,polymethylmethacrylate (“PMMA”), Parylene, Polyethylene terephthalate(“PET”), polyurethane, polyimide, rigid gas permeable fluorosiliconeacrylate, liquid crystal polymer, silicon-based polymers, siliconeacrylate and the like. Often, the polymer substrate 66, the glandstimulator assembly 20, and the sensor assembly 58 are encapsulated in asoft flexible biocompatible material 74 suitable for ocular wear, suchas polymeric material like PMMA, polyhydroxyethylmethacrylate(“polyHEMA”), silicone hydrogel, silicon based polymers (e.g.,flouro-silicon acrylate), silicone elastomer or combinations thereof.Generally, the device 10 is sufficiently flexible to be bent and placedunder the eyelid 45 and the lower lid 50 of the user 40. Generally, thering 15 forms a circular or ring shape with an uninterruptedcircumference or periphery. However, in some embodiments, a gap isformed within the ring 15 to form a C shape. In some embodiments, thedevice 10 may have a visual marker on the device to assist a user whenplacing the device 10 on the eye so that electrodes are orientedadjacent to the lacrimal gland.

Generally, the gland stimulator assembly 20 and the sensor assembly 58are operably coupled. Specifically, the sensor assembly 58 is operablycoupled to the microcontroller 22 of the gland stimulator assembly 20.In an example embodiment, any one or more portions or sub-parts of thegland stimulator assembly 20 and the sensor assembly 58 are operablycoupled. The device 10 may include any number of electrodes 21.

As illustrated in FIGS. 3 and 4, the microcontroller 22 is positionedbetween the sensors 58 a and 58 b such that the microcontroller 22 ispositioned between the lower lid 50 and the eye 35. In some embodiments,the cross-section of the ring 15 that is associated with themicrocontroller 22 is thicker or otherwise larger than othercross-sections of the ring 15. In some embodiments, the portion of thering 15 associated with the microcontroller 22 provides a friction-fitbetween the lower lid 50 and the eye 35 to anchor or position the ring15 such that the electrodes 21 are proximate to or aligned with thegland 55.

In some embodiments, the power source 24 is a battery or the like.However, in some embodiments the power source 24 is the user or isgenerated by movement of the user. For example, in some embodiments, thepower source is harvested energy from the body of the user 40 (e.g.,harvested from motion, temperature, both motion and temperature).

In some embodiments and as illustrated in FIGS. 5 and 6, the antenna 71is a looped antenna or a loop-shaped antenna that is formed within thering 15 or otherwise coupled to the ring 15.

Referring to FIG. 6 (lead assembly 23 not shown), when viewed from thefront view, the ring 15 is generally circular with a top point 15 bassociated with 0 degrees and an opposing bottom point 15 c associatedwith 180 degrees. Two midpoints 15 d and 15 e, between the top andbottom points 15 b and 15 c, are associated with 90 degrees and 270degrees respectively. In some embodiments, the sensor 58 a is positionedat or near the midpoint 15 d and the sensor 58 b is positioned at ornear the midpoint 15 e. Moreover, the microcontroller 22 is positionedat or near the bottom point 15 c with the electrodes 21 positionedbetween the midpoints 15 e and 15 b at a position associated betweenabout 300 degrees and about 0 degrees when the device 10 is designed forplacement in a right eye of the user 40. In some embodiments and whenthe device 10 is designed for placement in a left eye of the user 40,the electrodes 21 are positioned between the points 15 b and 15 dbetween about 0 degrees and about 60 degrees.

As illustrated in FIG. 7, the device 10 is configured to be chargedand/or cleaned by a remote device 80. Generally, the microcontroller 22is configured for wireless communication with a microcontroller 85 ofthe remote device 80 via a network 90. In some embodiments, the remotedevice 80 includes the microcontroller 85, a power source 95, a display100, and chambers 105 and 110 formed in a housing 112. Wirelessconnectivity may be provided by the microcontrollers 22 and 85, or atransceiver (not shown) coupled to each of the microcontrollers 22 and85. In some embodiments, the remote device 80 is configured totemporarily house the device 10 and a similar device 10′. In someembodiments, the devices 10 and 10′ are temporarily housed in thechambers 105 and 110, respectively, for cleaning of the sensor assembly58 and/or the gland stimulator assembly 20, for recharging of the powersource 24 such as recharging via the power source 95, and/or fortransmitting data between the microcontroller 22 and the microcontroller85. In some embodiments, the device 10 is associated with, or configuredfor, the right eye 35 of the user 40 and the device 10′ is configuredfor the left eye of the user 40. In some embodiments, themicrocontroller 22 is configured to communicate with another remotedevice 120 that includes a microcontroller 125, a power source 130, adisplay 135, and an alarm device 140. In some embodiments, the displays135 and 100 are omitted. In some embodiments, the remote device 120 is asmart phone, tablet computer, personal digital assistant (PDA), orpersonal computing device (PCDs), or the like. In some embodiments, dataexchanged between each of the devices 10 and 10′ and the remote device80 takes the form of any suitable technique, such as Bluetooth®, MICS,RF data, infrared, near field communication (NFC), etc. In someembodiments, the data exchanged includes or is related to the patientdata, such as for example the temporal model, an updated temporal model,external factors, and any other useful information for operating aclosed-loop therapy system.

FIG. 8 is a flow chart illustrating a method 200 of operating the device10 of FIGS. 1-7, according to an example embodiment. Generally, themethod 200 includes monitoring eye conditions of the user 40 at step205, determining whether to stimulate the lacrimal gland 55 at step 210,stimulating the lacrimal gland at step 215, storing patient data at step220, predicting future dry-eye symptoms at step 225, and generating analarm when dry-eye symptoms exceed a threshold at step 230.

At the step 205, and when the device 10 includes the sensor assembly 58,the device 10 detects the eye condition(s) of the patient or user 40 viathe sensor assembly 58. Generally, the sensor assembly 58 continuouslymonitors eye condition(s) of the user 40 to generate user eye conditiondata. In some embodiments, the sensor assembly 58 is used to detect adry eye condition based on the user eye condition data that includes:blink rate data generated by the sensor 58 d; TFBU time data generatedby the sensors 58 a and 58 b; and/or tear pH data generated by thesensor 58 d. In some embodiments, the device 10 monitors all threeparameters (i.e., blink rate, TFBU time, and tear pH), but in otherembodiments, any variation or combination of the three parameters iscontinuously or periodically monitored. In some embodiments, the usereye condition data forms a portion of the patient data that is stored inthe microcontroller 22. In other embodiments and when the sensorassembly 58 is omitted from the device, the eye condition(s) detectedduring the step 205 may be detected by the remote device 120 or anotherdevice.

At the step 210, the device 10 determines, using the user eye conditiondata (e.g., blink rate data, TFBU time data, and tear pH data), whetherto stimulate the gland 55 using the gland stimulator assembly 20. Asillustrated in FIG. 10, the step 210 can include the steps of receivingmonitored eye condition values via the user eye condition data,comparing the values with previous values, determining whether there hasbeen a threshold signal change to any metric, and then taking intoaccount external factors such as local environmental factors, healthfactors, and personalization factors. Upon receiving the monitored eyecondition values, the microcontroller 22 compares the most recentlyreceived values with historical or previously received values. In someembodiments, the microcontroller 22 determines a difference between therecently received values and the previous values. In some embodiments,the previous values are values received within a specific period of time(i.e., all previous values received in the last 2 hours), a specificnumber of most recently received values (i.e., the 1000 most recentlyreceived values), and/or the highest/lowest values received (i.e.,highest blink rate associated with the user). In other embodiments, oneof the previous values is a target value or baseline, and the differenceis calculated against the target value. The difference may be anincremental difference based on the most recent value or may be adifference calculated based on maximum, minimum, average, or target ofthe previously received values. After the difference is identified, themicrocontroller 22 determines if the difference exceeds a threshold.Generally, if the difference does not exceed the threshold, thenstimulation is not required. If the difference exceeds the threshold,then the microcontroller 22 continues to determine if stimulation isrequired. In summary, the use of sensors, such as sensor assembly 58, onor in the device 10 provides for closed-loop stimulation that involvescomparing measurements to desired values to determine whether and/or howto stimulate the lacrimal gland to yield tear production.

When determining if stimulation is required, the microcontroller 22considers external factors that include environmental factors, healthfactors, and personalization factors of the user 40. The environmentalfactors include the time of day, the season, the weather, etc. Thehealth factors include medications taken by the user 40, the hormones ofthe user 40 (administered or measured within the user 40), and the sleepcycle of the user 40. The personalization factors include whether theuser 40 is assumed to be studying, working, or performing anotheractivity. In some embodiments, the microcontroller 22 considers theexternal factors to determine whether exceeding the threshold isindicative of a true dry-eye symptom or is contributed to an externalfactor. For example, if the blink rate exceeds the threshold therebyindicating that a dry-eye symptom is present, but the user 40 isperforming an activity that results in a higher blink rate, then themicrocontroller 22 may determine that, in this instance, the blink rateexceeding the threshold does not correlate with a dry-eye symptom, butwith the activity of the user 40. Thus, the microcontroller 22 performsa factor-weighted analysis using the external factors to determinewhether the weighted difference exceeds the threshold and stimulation ofthe gland 55 is necessary or desired. However, in other embodiments andwhen the sensor assembly 58 is omitted from the device 10, the step 210includes referencing the temporal model stored in the memory 26 and/orreceiving instructions wirelessly.

At the step 215, the device 10 stimulates the gland 55 via theelectrodes 21. Upon stimulation, tears are produced principally by thelacrimal gland 55 under the influence of the parasympathetic andsympathetic nerves. Electrical stimulation of the afferent and efferentnerves proximal to the lacrimal gland 55 can elicit a tear response.Efferent fibers synapse directly with the lacrimal gland acinar cellsand trigger the release of water, electrolytes, and proteins from thelacrimal gland 55 onto the ocular surface. In some embodiments, thegland stimulator assembly 20 emits 10-100 Hz, 100-500 μs pulses, withcharge density of 0.05-5.0 μC mm−2. Stimulation can be applied throughbiphasic charge-balanced waveforms. In some embodiments, the targetstimulation parameters are modulated to achieve optimum response basedon several factors including the patient's own physiology andenvironmental variables. In some embodiments and before stimulating thegland 55 via the electrodes 21, the microcontroller calculates thefactor-weighted target stimulation parameters. That is, themicrocontroller 22 considers the external factors and historical patientdata to determine the strength and duration of stimulation that isrequired. In some embodiments, the historical patient data includes thepatient's response to historical gland stimulation. That is, themicrocontroller 22 monitored a change in the eye condition(s) using thesensor assembly 58 while simultaneously stimulating the lacrimal gland55 using previous target stimulation parameters. The detected change inthe eye condition(s) in response to stimulation using the previoustarget stimulation parameters forms a portion of the historical patientdata. Thus, the device 10 is capable of refining or updating theprevious target stimulation parameters to determine the targetstimulation parameters, based on the patient's response to previoussimulations. Moreover, the microcontroller 22 considers the externalfactors to determine the target stimulation parameters. That is, themicrocontroller 22 not only performs a factor-weighted analysis usingthe external factors to determine whether the stimulation is required,but also performs a factor-weighted analysis using the external factorsto determine the target stimulation parameters for the requiredstimulation. In some embodiments, the microcontroller 22 stores thetarget stimulation parameters and/or updates the temporal model usingthe target stimulation parameters before, during, or after stimulatingthe gland 55.

FIG. 10 illustrates a closed loop dry eye control system administered bythe device 10 during the steps 205, 210, and 215. As illustrated, baseis DryEye(t)_(base) the patient specific target tear hydration baseline.DryEye_(actual) is the real-time dry-eye condition as measured by thesensor assembly 58. In this embodiment the microcontroller 22, which insome embodiments includes or is a proportional-integral-derivative(“PID”) controller, first detects DryEye_(actual) via the monitored datafrom the sensor assembly 58 and adjusts the amount of lacrimalstimulation administered by the electrodes 21 proportional to themagnitude and direction of the deviation error from DryEye(t)_(base).The microcontroller 22 may compare against patient data recorded duringthe last 24 hours or month, for example. In some embodiments, themicrocontroller 22 compares against patient data recorded during thelast 24 hours, for example.

At step 220, the patient data, which includes the monitored data, thetarget stimulation parameters, the previous target stimulationparameters, and the external factors data (measured, assumed, orreceived by the user 40), is stored. As noted above, in someembodiments, the user/patient data is stored in the microcontroller 22.However, the user/patient data is also stored or received by themicrocontroller 85 of the remote device 80 via the network 90 and/orstored or received by the microcontroller 125 of the remote device 120via the network 90. As illustrated in FIG. 7, during standard devicedisinfection or charging times (e.g., weekly or monthly), themicrocontroller 22 may upload and update the user/patient data, whichmay span months to years, to a cloud-based database via themicrocontroller 85 and/or the microcontroller 125. This user/patientdata can be used to update, customize, and generate predictive models torefine dry eye management over the course of hours to days. The modelsmay include a variety of factors including historical, current, andexpected or predicted external factors, which are used to generatepredictive models. Thus, on-board prediction allows for optimizedpatient regimens, or temporal models, based on each patient's specificphysiology. These metrics may include patient-specific parameters suchas, for example, age, comorbidities, diabetes, hormonal changes(pregnancy, contraceptive use, and hormone replacement therapy),allergies, blink rate, tear generation rate, etc. In some embodiments,metrics also include monitoring medications and dosage (e.g., bloodpressure medications (diuretics and beta-blockers), sleeping pills,antidepressants, anti-anxiety drugs, painkillers, antihistamines, anddecongestants as well as some medications used to treat acne andParkinson's disease). In some embodiments, metrics also includeenvironmental factors such as, for example, dry indoor environments; airconditioning or heat; hospital environments; airplanes; other workenvironments; wind; smoke; fumes from chemicals; and sunlight. Patientmetrics and patient data, when used with predictive models, are used tocreate and provide customized treatment for each patient thatsimultaneously addresses symptoms and compliance, which generallyimproves outcomes for DED patients.

In some embodiments, the remote device 120 requests confirmation thatvalues classified as a dry-eye symptom coincided with a dry-eye symptom.The request for confirmation may be displayed on the display 135 of theremote device 120. The user 40 of the remote device 120 can provideconfirmation via an input button located on the remote device 120. Insome embodiments, a patient profile that includes the user/patient dataand customized treatment plans for the user 40 is stored in one or moreof the microcontrollers 22, 85, and/or 125 such that the patient profileis refined with every use of the device 10 by the user 40. In someinstances, and when the device 10 is disposable or has a limited designlife, the patient profile is stored in the microcontroller 85 or 125,and when a new device similar to the device 10 is paired with the remotedevice 80 or 120, the patient profile is capable of being uploaded ortransferred to the new device.

At the step 225, a future dry-eye symptom is predicted using themicrocontroller 22. Using historical user data and the patient profile,the microcontroller 22 identifies a trend of a value to predict anupcoming untreatable dry-eye symptom that may exceed the treatmentcapabilities of the device 10. In some embodiments, the device 10monitors the duration and frequency of values that are classified as adry-eye symptom and that are also treated or corrected via stimulationof the gland 55. The device 10 and/or the remote device 120 alsodetermines if the duration of the detected dry-eye symptom is greaterthan a predetermined maximum duration. For example, dry-eye symptomslasting longer than 2 hours (or another predetermined duration of timethat is associated with potential damage to the eye 35) may beclassified as a detected untreatable dry-eye symptom that requiresintervention by the user 40.

At the step 230 and in some embodiments, the remote device 120 generatesan alarm. Generally, the alarm is in response to the device 10 or theremote device 120 predicting and/or detecting an untreatable dry-eyesymptom. In some embodiments, the remote device 120 generates differenttypes of alarms, such as, for example the predicted or detecteduntreatable dry-eye symptom warning. Moreover, a first recommendationmay be generated as well. For example, the first recommendation may beto administer eye drops to avoid potential damage to the eye 35, changeambient conditions, change activity, and the like. The recommendationincludes an audible recommendation via a speaker (e.g., the alarm device140) of the remote device 120 and/or a written message displayed on thedisplay 135 of the remote device 120. In some embodiments, an alarm isgenerated by the device 10 without the remote device 120. For example,the device 10 may include a light-emitting diode which is activated togenerate the alert, the device 10 may provide a vibration alert, or thedevice 10 may provide an electrical pulse that produces a physicalsensation on the eye 35.

While in some embodiments the device 10 communicates with the remotedevice 80 and/or the remote device 120 when the device 10 is removedfrom periocular space, in other embodiments, the power source 24 isrecharged while the device 10 is worn by the user 40. For example, thepower source 24 could be charged by a power source that is positionedwithin a pair of glasses, hat, or ear piece that is capable of chargingthe power source 24 when worn by the user 40. In other embodiments, thedevice 10 communicates with the remote device 80 and/or the remotedevice 120 when the device 10 is worn by the user 40. In these cases,and when the remote device 120 is a phone or other mobile electronicdevice associated with the user 40, GPS data of the remote device 120,and thus the user 40, is communicated to the microcontroller 22. In someembodiments, the real-time location via the GPS data of the user 40 isconsidered by the microcontroller 22 as an external factor. In someembodiments, data received and monitored by the remote device 120 iscommunicated to the microcontroller 22 and is one of the externalfactors. In other embodiments, GPS data is considered by themicrocontroller 125 when determining/updating the patient profile, whichis then uploaded to the device 10. However, other types of locationinformation, such as calendar event based means, cellular triangulation,WIFI source, user input, etc., can be considered by the microcontroller125 and uploaded to the device.

In some embodiments, the electrodes 21 are spaced between the midpoints15 d and 15 e such that the point 15 b is positioned between electrodes21. In some instances, the electrodes 21 are spaced around the entiretyof the circumference of the ring 15. In some embodiments, themicrocontroller 22 learns via selective stimulation of portions of theelectrodes 21 whether the device 10 is positioned in the right or lefteye and selectively activates the portion of the electrodes 21 that havebeen determined as proximate the lacrimal gland 55. Thus, one design ofthe device 10 is capable of being used in either eye of the user 40.

In some embodiments, the device 10 and/or the method 200 responds to thepatient's current physiological state and provides optimum therapeuticstimulation of the lacrimal gland 55. In some embodiments, the device 10and/or the method 200 does not block or affect vision in any way as thelimbal ring 60 and an iris of the eye 35 extend through and beyond theopening of the ring 15. In some embodiments, the device 10 and/or themethod 200 is compatible with all forms of vision correction (e.g.,contact lenses, spectacles, etc.). In some embodiments, the device 10and/or the method 200 generates data used for improved outcomes-basedcare models. In some embodiments, the device 10 and/or the method 200targets stimulations both temporally and spatially to the lacrimal gland55. In some embodiments, the device 10 and/or the method 200 can be usedto achieve fully customizable stimulation paradigms from first-orderconstant stimulation profiles to on-demand pulsatile stimulation.Factors considered by the device 10 and/or the method 200 includecircadian, seasonal, behavioral, and slowly varying variables that arecurrently not factored in any useful way into the management of dry eye.In some embodiments, the device 10 and/or the method 200 providesambulatory hands-free and automatic operation that is invisible to thepatient and others. In some embodiments, the device 10 and/or the method200 monitors and treats dry eye discreetly without tethering or anyadditional body worn hardware. Generally, the device 10 allows forintegrated dry-eye sensing, integrated, hands-free electronic lacrimalgland stimulation, and closed-loop operation based on patient-specificphysiological parameters and personalized environmental and healthfactors.

In other embodiments, the microcontroller 125 is a battery operated hubwith a processor. In other embodiments, the microcontroller 125 isomitted or replaced with a remote server (e.g., “the cloud”). Moreover,in some embodiments, the device 10 is at least capable of communicatingwith an application server. In some embodiments, a mobile application isstored in the memory of the microcontroller 125, and selectivelydisplayed on the display 135, of the remote device 120 and/or in thememory, and selectively displayed on the display 100 of the remotedevice 80. The mobile application is in communication with theapplication server via the network 90. The user data and/or a summarythereof is received by the application server directly from the device10 via the network 90. In some embodiments, the application serverpredicts/detects a potential dry-eye symptom that exceeds a maximumthreshold amount and sends instructions to generate the alert to theremote device 120. In some embodiments, the alert includes a pushnotification displayed on the display 135 of the remote device 120.Thus, while the collection of the user data is performed at the device10, there are multiple locations at which the predicting/detecting canoccur, such as, for example, in the microcontroller 125 of the remotedevice 120, in the microcontroller 22, or in a remote server.

In some embodiments, the measurements and combinations of measurementsthat are classified as an indication of dry-eye symptom are refinedbased upon an aggregation of data from multiple users, with the datahaving been received at the remote server. That is, in some embodiments,data from multiple users can be used to refine the factor-weightedanalysis performed by the microcontrollers 22, 85, and/or 125.

In some embodiments, the device 10, the remote device 80, and/or theremote device 120 are configured to operate in a sleep or idle mode.

In some embodiments and as noted above, the sensor assembly 58 isomitted from the device 10 and the microcontroller 22 activates theelectrodes 21 based on a predetermined schedule that is stored in thedevice 10, regardless of the eye conditions. In some embodiments, thesensor assembly 58 is omitted from the device 10 and the microcontroller22 activates the electrodes 21 in response to a wireless transmission orcommand from the remote device 120. That is, the remote device 120 maybe monitoring conditions and wirelessly instructing the microcontroller22 to activate the electrodes 21. As such and in some embodiments, theremote device 120 includes a sensor assembly, such as a camera, whichmeasures the eye conditions of the user. For example, and when the useris looking at the remote device 120, the remote device 120 detects ablink rate that indicates a dry-eye condition and the remote device 120instructs the microcontroller 22 to activate the electrodes 21.

In an example embodiment, the network 90 includes the Internet, one ormore local area networks, a Bluetooth low energy network, one or morewide area networks, one or more cellular networks, one or more wirelessnetworks, one or more voice networks, one or more data networks, one ormore communication systems, and/or any combination thereof.

Generally, any creation, storage, processing, and/or exchange of userdata associated the method, apparatus, and/or system disclosed herein isconfigured to comply with a variety of privacy settings and securityprotocols and prevailing data regulations, consistent with treatingconfidentiality and integrity of user data as an important matter. Forexample, the apparatus and/or the system may include a module thatimplements information security controls to comply with a number ofstandards and/or other agreements. In some embodiments, the modulereceives a privacy setting selection from the user and implementscontrols to comply with the selected privacy setting. In otherembodiments, the module identifies data that is considered sensitive,encrypts data according to any appropriate and well-known method in theart, replaces sensitive data with codes to pseudonymize the data, andotherwise ensures compliance with selected privacy settings and datasecurity requirements and regulations.

In some embodiments, the device 10 automatically, dynamically, andpredictively adjusts therapeutic levels of DED treatment throughout theday/week/month based on real-time measurement of the patient's dry-eyephysiology leveraged against personalized environmental and healthfactors. With electronics integration into the periocular-mounted device10, patient specific therapies are tailored through direct measurementof physiological indicators such as blink rate, tear film break-up timeand tear pH that are monitored by the sensor assembly 58. In someembodiments, the sensor assembly 58 includes—in addition to as asubstitute for the sensors 58 a, 58 b, 58 c, and 58 d—one or morethermal sensors that monitors the eye surface temperature, one or moresensors that monitors the meibum content (i.e., the oils that preventrapid tear evaporation), and/or one or more sensors that monitor cornealand conjunctival inflammation biomarkers.

In an example embodiment, as illustrated in FIG. 11 with continuingreference to FIGS. 1-10, an illustrative node 1000 for implementing oneor more of the example embodiments described above and/or illustrated inFIGS. 1-10 is depicted. The node 1000 includes a microprocessor 1000 a,an input device 1000 b, a storage device 1000 c, a video controller 1000d, a system memory 1000 e, a display 1000 f, and a communication device1000 g all interconnected by one or more buses 1000 h. In severalexample embodiments, the storage device 1000 c may include a hard drive,CD-ROM, optical drive, any other form of storage device and/or anycombination thereof. In several example embodiments, the storage device1000 c may include, and/or be capable of receiving, a CD-ROM, DVD-ROM,or any other form of computer-readable medium that may containexecutable instructions. In several example embodiments, thecommunication device 1000 g may include a modem, network card, or anyother device to enable the node to communicate with other nodes. Inseveral example embodiments, any node represents a plurality ofinterconnected (whether by intranet or Internet) computer systems,including without limitation, personal computers, mainframes, PDAs,smartphones, and cell phones.

In several example embodiments, one or more of the components of thesystems described above and/or illustrated in FIGS. 1-10, include atleast the node 1000 and/or components thereof, and/or one or more nodesthat are substantially similar to the node 1000 and/or componentsthereof.

In several example embodiments, one or more of the applications,systems, and application programs described above and/or illustrated inFIGS. 1-10, include a computer program that includes a plurality ofinstructions, data, and/or any combination thereof; an applicationwritten in, for example, Arena, Hypertext Markup Language (HTML),Cascading Style Sheets (CSS), JavaScript, Extensible Markup Language(XML), asynchronous JavaScript and XML (Ajax), and/or any combinationthereof; a web-based application written in, for example, Java or AdobeFlex, which in several example embodiments pulls real-time informationfrom one or more servers, automatically refreshing with latestinformation at a predetermined time increment; or any combinationthereof.

In several example embodiments, a computer system typically includes atleast hardware capable of executing machine readable instructions, aswell as the software for executing acts (typically machine-readableinstructions) that produce a desired result. In several exampleembodiments, a computer system may include hybrids of hardware andsoftware, as well as computer subsystems.

In several example embodiments, hardware generally includes at leastprocessor-capable platforms, such as client-machines (also known aspersonal computers or servers), and hand-held processing devices (suchas smartphones, tablet computers, personal digital assistants (PDAs), orpersonal computing devices (PCDs), for example). In several exampleembodiments, hardware may include any physical device that is capable ofstoring machine-readable instructions, such as memory or other datastorage devices. In several example embodiments, other forms of hardwareinclude hardware subsystems, including transfer devices such as modems,modem cards, ports, and port cards, for example.

In several example embodiments, software includes any machine codestored in any memory medium, such as RAM or ROM, and machine code storedon other devices (such as flash memory, or a CD ROM, for example). Inseveral example embodiments, software may include source or object code.In several example embodiments, software encompasses any set ofinstructions capable of being executed on a node such as, for example,on a client machine or server.

In several example embodiments, combinations of software and hardwarecould also be used for providing enhanced functionality and performancefor certain embodiments of the present disclosure. In an exampleembodiment, software functions may be directly manufactured into asilicon chip. Accordingly, it should be understood that combinations ofhardware and software are also included within the definition of acomputer system and are thus envisioned by the present disclosure aspossible equivalent structures and equivalent methods.

In several example embodiments, computer readable mediums include, forexample, passive data storage, such as a random-access memory (RAM) aswell as semi-permanent data storage such as a compact disk read onlymemory (CD-ROM). One or more example embodiments of the presentdisclosure may be embodied in the RAM of a computer to transform astandard computer into a new specific computing machine. In severalexample embodiments, data structures are defined organizations of datathat may enable an embodiment of the present disclosure. In an exampleembodiment, a data structure may provide an organization of data, or anorganization of executable code.

In several example embodiments, any networks and/or one or more portionsthereof may be designed to work on any specific architecture. In anexample embodiment, one or more portions of any networks may be executedon a single computer, local area networks, client-server networks, widearea networks, internets, hand-held and other portable and wirelessdevices, and networks.

In several example embodiments, a database may be any standard orproprietary database software. In several example embodiments, thedatabase may have fields, records, data, and other database elementsthat may be associated through database specific software. In severalexample embodiments, data may be mapped. In several example embodiments,mapping is the process of associating one data entry with another dataentry. In an example embodiment, the data contained in the location of acharacter file can be mapped to a field in a second table. In severalexample embodiments, the physical location of the database is notlimiting, and the database may be distributed. In an example embodiment,the database may exist remotely from the server and run on a separateplatform. In an example embodiment, the database may be accessibleacross the Internet. In several example embodiments, more than onedatabase may be implemented.

In several example embodiments, a plurality of instructions stored on anon-transitory computer readable medium may be executed by one or moreprocessors to cause the one or more processors to carry out or implementin whole or in part the above-described operation of each of theabove-described example embodiments of the system, the method, and/orany combination thereof. In several example embodiments, such aprocessor may include one or more of the microprocessor 1000 a, anyprocessor(s) that are part of the components of the system, and/or anycombination thereof, and such a computer readable medium may bedistributed among one or more components of the system. In severalexample embodiments, such a processor may execute the plurality ofinstructions in connection with a virtual computer system. In severalexample embodiments, such a plurality of instructions may communicatedirectly with the one or more processors, and/or may interact with oneor more operating systems, middleware, firmware, other applications,and/or any combination thereof, to cause the one or more processors toexecute the instructions.

A periocular ring configured to be worn on an eye of a user is disclosedthat includes a plurality of electrodes spaced along the periocularring; a microcontroller; and a lead assembly extending along at least aportion of the periocular ring; wherein the lead assembly extendsbetween the microcontroller and the plurality of electrodes to operablycouple the plurality of electrodes to the microcontroller; and whereinthe microcontroller is configured to activate the plurality ofelectrodes via the lead assembly to stimulate a lacrimal gland of theuser. In one embodiment, the plurality of electrodes is spacedcircumferentially along the periocular ring. In one embodiment, theplurality of electrodes is spaced radially along the periocular ring. Inone embodiment, the plurality of electrodes is spaced circumferentiallyalong a cross-section of the periocular ring. In one embodiment, theperiocular ring has an opening that defines an innermost diameter; andwherein, when the periocular ring is worn on the eye of the user, aportion of the eye extends through the opening of the periocular ring.In one embodiment, the innermost diameter is greater than a diameter ofa limbal ring of the eye. In one embodiment, the microcontroller isconfigured to activate the electrodes based on a temporal model thatcomprises a target magnitude, a target frequency, and a target pulsewidth of output pulse(s) applied to the plurality of electrodes; and thetemporal model is based on a user profile associated with the user. Inone embodiment, the ring includes a power source operably coupled to themicrocontroller and the plurality of electrodes to supply the outputpulse(s) applied to the plurality of electrodes.

A periocular assembly configured to be worn on an eye of a user andcircumscribe an iris of the user is disclosed and includes a pluralityof electrodes spaced along the periocular assembly; a firstmicrocontroller comprising a memory, wherein a temporal model associatedwith the user is stored in the memory; and a lead assembly extendingalong at least a portion of the periocular assembly; wherein the leadassembly extends between the first microcontroller and the plurality ofelectrodes to operably couple the plurality of electrodes to the firstmicrocontroller; wherein the periocular assembly is positioned in theupper and lower fornix of the eye of the user such that the plurality ofelectrodes is proximate a lacrimal gland of the user. In one embodiment,the first microcontroller is configured to activate the plurality ofelectrodes to stimulate the lacrimal gland of the user based on thetemporal model associated with the user; the periocular assembly furthercomprises a second microcontroller that is spaced from the periocularassembly; and the second microcontroller is configured to: update thetemporal model associated with the user based on external factorsassociated with the user; wherein the external factors associated withthe user comprises: data associated with health factors associated withthe user; data associated with environmental factors associated with alocal environment of the user, and/or activity data associated withactivities performed by the user; and transmit the temporal model to thefirst microcontroller. In one embodiment, the periocular assembly has anopening that defines an innermost diameter; and when the periocularassembly is worn on the eye of the user, a portion of the eye extendsthrough the opening of the periocular assembly. In one embodiment, theinnermost diameter is greater than a diameter of a limbal ring of theeye. In one embodiment, the plurality of electrodes is spacedcircumferentially along the periocular assembly. In one embodiment, theplurality of electrodes is spaced radially along the periocularassembly. In one embodiment, the plurality of electrodes is spacedcircumferentially along a cross-section of the periocular assembly.

A method of stimulating a lacrimal gland of a user using a perioculardevice is disclosed and includes positioning the periocular devicebetween an eyelid and an eye of the user; wherein the periocular devicecomprises: a ring configured to be worn on the eye of the user; and astimulator assembly comprising: a plurality of electrodes spaced alongthe ring; a microcontroller comprising a memory, wherein stimulationparameters are stored in the memory; and a lead assembly extending alongat least a portion of the ring; wherein the lead assembly extendsbetween the microcontroller and the plurality of electrodes to operablycouple the plurality of electrodes to the microcontroller; wherein theperiocular device is positioned in the eye of the user such that theplurality of electrodes is proximate the lacrimal gland of the user; andactivating, using the microcontroller and based on the stimulationparameters, the plurality of electrodes to stimulate the lacrimal glandof the user. In one embodiment, the plurality of electrodes is spacedcircumferentially along the ring. In one embodiment, the plurality ofelectrodes is spaced radially along the ring. In one embodiment, theplurality of electrodes is spaced circumferentially along across-section of the ring. In one embodiment, the ring has an openingthat defines an innermost diameter; and wherein, when the ring is wornon the eye of the user, a portion of the eye extends through the openingof the ring. In one embodiment, the innermost diameter is greater than adiameter of a limbal ring of the eye. In one embodiment, the stimulationparameters comprise a target magnitude, a target frequency, and a targetpulse width of output pulse(s) applied to the electrodes; andactivating, using the microcontroller and based on the stimulationparameters, the plurality of electrodes comprises activating theplurality of electrodes via output pulse(s) at the target magnitude, attarget frequency, and at target pulse width. In one embodiment, thestimulation parameters are based on a user profile associated with theuser. In one embodiment, the stimulation parameters comprise apredetermined stimulation schedule; and wherein activating, using themicrocontroller, and based on the stimulation parameters, the pluralityof electrodes to stimulate the lacrimal gland of the user is inaccordance with the predetermined stimulation schedule.

It is understood that variations may be made in the foregoing withoutdeparting from the scope of the present disclosure.

In several example embodiments, the elements and teachings of thevarious illustrative example embodiments may be combined in whole or inpart in some or all of the illustrative example embodiments. Inaddition, one or more of the elements and teachings of the variousillustrative example embodiments may be omitted, at least in part,and/or combined, at least in part, with one or more of the otherelements and teachings of the various illustrative embodiments.

Any spatial references such as, for example, “upper,” “lower,” “above,”“below,” “between,” “bottom,” “vertical,” “horizontal,” “angular,”“upwards,” “downwards,” “side-to-side,” “left-to-right,”“right-to-left,” “top-to-bottom,” “bottom-to-top,” “top,” “bottom,”“bottom-up,” “top-down,” etc., are for the purpose of illustration onlyand do not limit the specific orientation or location of the structuredescribed above.

In several example embodiments, while different steps, processes, andprocedures are described as appearing as distinct acts, one or more ofthe steps, one or more of the processes, and/or one or more of theprocedures may also be performed in different orders, simultaneouslyand/or sequentially. In several example embodiments, the steps,processes and/or procedures may be merged into one or more steps,processes and/or procedures.

In several example embodiments, one or more of the operational steps ineach embodiment may be omitted. Moreover, in some instances, somefeatures of the present disclosure may be employed without acorresponding use of the other features. Moreover, one or more of theabove-described embodiments and/or variations may be combined in wholeor in part with any one or more of the other above-described embodimentsand/or variations.

Although several example embodiments have been described in detailabove, the embodiments described are example only and are not limiting,and those skilled in the art will readily appreciate that many othermodifications, changes and/or substitutions are possible in the exampleembodiments without materially departing from the novel teachings andadvantages of the present disclosure. Accordingly, all suchmodifications, changes and/or substitutions are intended to be includedwithin the scope of this disclosure as defined in the following claims.In the claims, any means-plus-function clauses are intended to cover thestructures described herein as performing the recited function and notonly structural equivalents, but also equivalent structures. Moreover,it is the express intention of the applicant not to invoke 35 U.S.C. §112, paragraph 6 for any limitations of any of the claims herein, exceptfor those in which the claim expressly uses the word “means” togetherwith an associated function.

What we claim is:
 1. A method of stimulating a lacrimal gland of a userusing a periocular assembly positioned in a fornix of an eye of theuser; wherein the periocular assembly comprises; a ring configured to beworn in a periocular space of the user; a plurality of stimulatingelectrodes coupled to the ring; a microcontroller operably coupled tothe plurality of stimulating electrodes; and a sensor assembly coupledto the ring and operably coupled to the microcontroller; wherein themethod comprises; obtaining, from the sensor assembly, first datarepresentative of an eye condition; obtaining, from a memory of a mobilecomputing device, second data representative of external factorsassociated with at least one of the user or an environment; andactivating, using the microcontroller and based on the first datarepresentative of the eye condition and the second data representativeof the external factors, the plurality of stimulating electrodes.
 2. Themethod of claim 1, wherein the obtaining the first data comprisestransmitting, by the periocular assembly to the mobile computing device,the first data, wherein the obtaining the second data comprisesobtaining, by a processor of the mobile computing device, the seconddata from the memory, and wherein the method further comprises:receiving, by the periocular assembly from the mobile computing device,a signal activating the plurality of stimulating electrodes.
 3. Themethod of claim 1, wherein the obtaining the first data comprisesobtaining, by the microcontroller of the periocular assembly, the firstdata, and wherein the obtaining the second data comprises receiving, bythe periocular assembly from the mobile computing device, the seconddata.
 4. The method of claim 1, wherein the first data comprises atleast one of: data associated with health factors associated with theuser; data associated with environmental factors associated with a localenvironment of the user; and activity data associated with activitiesperformed by the user.
 5. The method of claim 1, further comprising thesteps of: comparing, using the microcontroller, a target eye conditionto at least one of the first data and the second data to determine adifference; determining, using the microcontroller based on thedifference, target stimulation parameters; monitoring a change in theeye condition using the sensor assembly after activating the pluralityof stimulating electrodes using the target stimulation parameters; andupdating the target stimulation parameters in response to the change inthe eye condition, wherein the activating the plurality of stimulatingelectrodes is further based on the target stimulation parameters.
 6. Themethod of claim 5, wherein the target stimulation parameters comprise atarget magnitude, a target frequency, and a target pulse width of outputpulse(s) applied to the plurality of stimulating electrodes; and whereinthe activating the plurality of stimulating electrodes comprisesactivating the plurality of stimulating electrodes via output pulse(s)based on the target magnitude, the target frequency, and the targetpulse width.
 7. The method of claim 1, wherein the sensor assemblycomprises at least one of: an electrode configured for measuringresistivity of a tear fluid of the user; a microelectrode pH sensorconfigured for measuring a pH level of the tear fluid; or a resonantcircuit configured for measuring a blink rate of the user.
 8. The methodof claim 7, wherein the sensor assembly comprises the resonant circuit;wherein the resonant circuit comprises an inductive loop and acapacitor; and wherein the inductive loop and the capacitor areconfigured for detecting movement of an eyelid of the user.
 9. Themethod of claim 1, further comprising generating, based on the firstdata and the second data, a predictive model relating to a predictedfuture eye condition of the user.
 10. A device configured to be worn onthe eye of a user for stimulating a lacrimal gland, comprising: a ringconfigured to be worn in a periocular space of the user; a plurality ofstimulating electrodes coupled to the ring; a microcontroller operablycoupled to the plurality of stimulating electrodes; and a sensorassembly coupled to the ring and operably coupled to themicrocontroller; wherein the microcontroller is configured to: obtain,from the sensor assembly, first data representative of an eye condition;transmit the first data to a mobile computing device; receive, from themobile computing device, a signal based on the first data and seconddata representative of external factors associated with at least one ofthe user or an environment; and activate the plurality of stimulatingelectrodes based on the signal.
 11. The device of claim 10, wherein theexternal factors comprise any one or more of: data associated withhealth factors associated with the user; data associated withenvironmental factors associated with a local environment of the user;and, activity data associated with activities performed by the user. 12.The device of claim 10, wherein the microcontroller is configured to:compare a target eye condition to at least one of the first data and thesecond data to determine a difference; determine, based on thedifference, target stimulation parameters; activate the plurality ofstimulating electrodes based on the target stimulation parameters;monitor a change in the eye condition using the first data afteractivating the plurality of stimulating electrodes using the targetstimulation parameters; and update the target stimulation parameters inresponse to the change in the eye condition.
 13. The device of claim 10,wherein the sensor assembly comprises at least one of: an electrodeconfigured for measuring resistivity of a tear fluid of the user; amicroelectrode pH sensor configured for measuring a pH level of the tearfluid; or a resonant circuit configured for measuring a blink rate ofthe user.
 14. The device of claim 13, wherein the sensor assemblycomprises the resonant circuit; wherein the resonant circuit comprisesan inductive loop and a capacitor; and wherein the inductive loop andthe capacitor are configured for detecting movement of an eyelid of theuser.
 15. The device of claim 10, wherein the ring comprises an openingthat defines an innermost diameter; and wherein the opening isconfigured to receive a portion of the eye.
 16. The device of claim 15,wherein the innermost diameter is greater than a diameter of a limbalring of the eye.
 17. The device of claim 10, wherein the microcontrolleris configured to generate, based on the first data and the second data,a predictive model relating to a predicted future eye condition of theuser.
 18. The device of claim 17, wherein the microcontroller isconfigured to activate the plurality of stimulating electrodes based onthe predicted future eye condition of the user.
 19. A system forstimulating a lacrimal gland of an eye, the system, comprising: awearable device configured to be worn on the eye, the wearable devicecomprising: a ring configured to be worn in a periocular space of theuser; a plurality of stimulating electrodes coupled to the ring; amicrocontroller operably coupled to the plurality of stimulatingelectrodes; and a sensor assembly coupled to the ring and operablycoupled to the microcontroller; wherein the microcontroller isconfigured to: obtain, from the sensor assembly, first datarepresentative of an eye condition; transmit the first data to a mobilecomputing device; receive, from the mobile computing device, a signalbased on the first data and second data representative of externalfactors associated with at least one of the user or an environment; andactivate the plurality of stimulating electrodes based on the signal;and the mobile computing device, wherein the mobile computing devicecomprises: a memory; a transceiver configured to communicate with themicrocontroller of the wearable device; and a processor in communicationwith the memory and the transceiver.
 20. The system of claim 19, whereinthe processor of the mobile computing device is configured to: compare atarget eye condition to at least one of the first data and the seconddata to determine a difference; determine, based on the difference,target stimulation parameters; transmit, to the wearable device, asignal to activate the plurality of stimulating electrodes based on thetarget stimulation parameters; monitor a change in the eye conditionusing the first data after activating the plurality of stimulatingelectrodes using the target stimulation parameters; and update thetarget stimulation parameters in response to the change in the eyecondition.